A tailless Fas-FADD death-effector domain chimera is sufficient to executeFas function in T cells but not B cells of MRL-lpr/lpr mice

The Fas receptor delivers signals crucial for lymphocyte apoptosis through its cytoplasmic death domain. Several Fas cytoplasmic-associated proteins h ave been reported and studied in cell lines, So far, only as-associated dea th domain protein (FADD), another death domain-containing molecule has been shown to be essential for Fas signals in vivo. FADD is thought to function by recruiting caspase-8 through its death-effector domain. To test whether FADD is sufficient to deliver Fas signals, we generated transgenic mice ex pressing a chimera comprised of the Fas extracellular domain and FADD death -effector domain. Expression of this protein in lymphocytes of Far-deficien t MRL-lpr/lpr mice completely diminishes their T cell but not their B cell abnormalities. These results suggest that FADD alone is sufficient for init iation of Fas signaling in primary T cells, but other pathways may operate in B cells.